The use of gabapentinoids and opioids and risk of developing opioid-induced respiratory depression among older breast cancer survivors with neuropathic pain

Purpose: To estimate the combined effect of gabapentinoid and opioid therapy compared to opioid monotherapy on the risk of developing opioid-induced respiratory depression among breast cancer survivors with neuropathic pain.

Method: A nested case-control study of Medicare female breast cancer survivors with neuropathic pain receiving both opioids and gabapentinoids, opioid monotherapy, gabapentinoid monotherapy, and none of these drugs was conducted using SEER-Medicare between 2007 and 2015. Cases were survivors with respiratory depression and were matched with controls on the event date (± 1 year), age at diagnosis (± 5 years), and stage at diagnosis. Exposure to opioids and gabapentinoids was assessed 120 days before the event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls.

Results: A total of 657 cases and 11,471 controls were identified. After matching, 656 cases and 5612 controls were retained, and cases were more likely to be diagnosed with mental health disorders (24.4% vs 10.5%, p < 0.0001) than controls. In the primary adjusted analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to opioid monotherapy (Adj. OR: 1.513; 95% CI: 1.473-2.350). Additionally, under secondary analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to receiving neither of these classes. (Adj. OR: 1.595; 95% CI: 1.050-2.421).

Conclusion: There is a need for dose titration strategies of gabapentinoids and caution when co-prescribing opioids and gabapentinoids in older cancer survivors.